Physiologic and Genetic Contributions of Impaired Fetal Brain Development in Congenital Heart Disease

先天性心脏病胎儿大脑发育受损的生理和遗传贡献

基本信息

  • 批准号:
    9895856
  • 负责人:
  • 金额:
    $ 18.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-04-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Congenital heart disease (CHD) is the most common birth defect and, as survival has improved for patients with moderate-severe CHD, adults now outnumber children with this diagnosis. This reduction in mortality has shifted research focus to improving long-term outcomes and quality of life. The most common adverse outcome is neurodevelopmental impairment and occurs in 50% of patients with moderate-severe CHD. While postnatally measured medical and surgical factors play a crucial role in the care and outcomes of these infants, brain magnetic resonance imaging (MRI) studies have identified impaired brain development even before cardiac surgery and have emphasized the fetal period as a time when these abnormalities are evolving. These data suggest fetal interventions may be an important aspect of improving the high rates of neurodevelopmental impairments in CHD. The National Heart, Lung, and Blood Institute has highlighted a need for research focused on preventive and therapeutic strategies for reducing neurodevelopmental deficits in CHD. This Mentored Patient-Oriented Career Development Award aligns well with this need by aiming to characterize the trajectory of disrupted cortical brain development in fetuses with moderate-severe CHD and to understand mechanistic interactions between physiologic and genetic variation that underlie brain disruption in this population. These data will assist in identifying the timing and population of CHD fetuses that may benefit from fetal neuroprotective interventions and will inform risk prediction for patient counseling. This Award will provide the candidate the education, training, and mentoring necessary to successfully undertake this proposal and to develop the skills required to become an independent clinician scientist focused on improving neurodevelopmental outcomes in patients with CHD. Dr. Ortinau has already developed expertise in MR analysis techniques. Thus, the training and mentorship for this award will focus on: 1) enhancing knowledge of fetal cardiac physiology and developing expertise in the association of cardiac physiology with cerebral hemodynamics and fetal brain development; and 2) gaining knowledge and experience in genetic and genomic research to understand the contribution of genetic variation to cerebral cortical development. The unique environment at Washington University School of Medicine provides the opportunity to train in these key areas using the infrastructure, resources, and mentorship outlined in the candidate’s Career Development Plan. These research activities will provide the preliminary data necessary for development of an hypothesis-driven R01 application in Year 2 of this Award, aimed at understanding mechanistic interactions between physiologic and genetic pathways that may underlie disruption of brain development in moderate-severe CHD.
项目摘要 先天性心脏病(CHD)是最常见的出生缺陷,随着先天性心脏病患者的生存率提高, 中重度冠心病,成人现在超过了儿童,这种诊断。这种死亡率的降低已经转变为 研究重点是改善长期结果和生活质量。最常见的不良后果是 神经发育障碍,发生在50%的中重度CHD患者中。虽然出生后 测量的医疗和手术因素在这些婴儿的护理和结果中起着至关重要的作用, 磁共振成像(MRI)研究已经发现,即使在心脏病发作之前, 手术,并强调胎儿期作为一个时间,当这些异常的发展。这些数据 这表明胎儿干预可能是改善神经发育不良率的一个重要方面。 CHD的损害。国家心脏、肺和血液研究所强调了研究重点的必要性。 减少CHD神经发育缺陷的预防和治疗策略。此指导 以患者为导向的职业发展奖旨在描述职业发展轨迹, 中重度CHD胎儿大脑皮质发育受损的机制, 生理和遗传变异之间的相互作用,这些变异是这一人群大脑中断的基础。这些 数据将有助于确定CHD胎儿的时间和人群, 干预措施,并将告知患者咨询的风险预测。 该奖项将为候选人提供成功开展工作所需的教育,培训和指导 这一建议,并发展所需的技能,成为一个独立的临床科学家,重点是提高 CHD患者的神经发育结局。Ortinau博士已经在MR分析方面积累了专业知识 技术.因此,该奖项的培训和指导将集中在:1)提高对胎儿的认识, 心脏生理学和发展心脏生理学与脑 血液动力学和胎儿大脑发育; 2)获得遗传和基因组学方面的知识和经验 研究以了解遗传变异对大脑皮层发育的贡献。独特的 华盛顿大学医学院的环境提供了在这些关键领域进行培训的机会 利用候选人职业发展计划中概述的基础设施、资源和指导。这些 研究活动将为开发一个假设驱动的R 01提供必要的初步数据 该奖项的第二年的应用,旨在了解生理和 可能导致中重度CHD患者大脑发育中断的遗传途径。

项目成果

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Cynthia Marie Ortinau其他文献

Cynthia Marie Ortinau的其他文献

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{{ truncateString('Cynthia Marie Ortinau', 18)}}的其他基金

Physiologic and Genetic Contributions of Impaired Fetal Brain Development in Congenital Heart Disease
先天性心脏病胎儿大脑发育受损的生理和遗传贡献
  • 批准号:
    10399424
  • 财政年份:
    2019
  • 资助金额:
    $ 18.17万
  • 项目类别:

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